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Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 199 records · Page 11Linked to original sources
PubMed2001

A flexible light-directed DNA chip synthesis gated by deprotection using solution photogenerated acids.

Oligonucleotide microarrays or oDNA chips are effective decoding and analytical tools for genomic sequences and are useful for a broad range of applications. Therefore, it is desirable to have synthesis methods of DNA chips that are highly flexible in sequence design and provide high quality and general adoptability. We report herein, DNA microarray synthesis based on a flexible biochip method. Our method simply uses photogenerated acid (PGA) in solution to trigger deprotection of the 5'-OH group in conventional nucleotide phosphoramidite monomers (i.e. PGA-gated deprotection), with the rest of the reactions in the synthesis cycle the same as those used for routine synthesis of oligonucleotides. The complete DNA chip synthesis process is accomplished on a regular DNA synthesizer that is coupled with a UV-VIS projection display unit for performing digital photolithography. Using this method, oDNA chips containing probes of newly discovered genes can be quickly and easily synthesized at high yields in a conventional laboratory setting. Furthermore, the PGA-gated chemistry should be applicable to microarray syntheses of a variety of combinatorial molecules, such as peptides and organic molecules.

DNA↗
PubMed2001

[Application of plasma radio frequency at low temperature in treatment of snoring and obstructive sleep apnea syndrome: a pilot study].

OBJECTIVE: To explore the effect of plasma radiofrequency at low temperature in treatment of snoring and obstructive sleep apnea syndrome (OSAS). METHODS: Plastic surgery of uvula and soft palate was performed by plasma radiofrequency at low temperature under local anaesthesia in out-patient department among 12 patients with simple snoring and 47 patients with OSA (42 males and 17 females with the average age of 40.2 +/- 7.2 years). Nocturnal polysomnography was performed before and after operation. The patients were followed up for 4 to 8 weeks after operation. RESULTS: Clinical symptoms improved significantly after four to eight weeks. The free margin of soft palate was elevated, the uvula was shortened, and the volume of tonsils was reduced remarkably. The pharyngeal space was expanded significantly. No bleeding, choke, open rhinolalia and cicatricial stricture occurred during and after operation. Mean AHI of 47 OSA patients decreased from 18.1 +/- 7.3 to 6.9 +/- 5.4 (P < 0.02), mean lowest SaO2 increased from 82.1% +/- 6.7% to 86.7% +/- 3.3% (P < 0.05). The percentage of slow wave sleep in total sleep time increased from 3.0 +/- 2.7% to 10.4 +/- 3.6% ( P < 0.05). In general, 49 patients were with excellent curative effect, 8 with good effect, and 2 needed oral appliance to release the base of tongue. Conclusion Snoring and mild and moderate obstructive sleep apnea can be significantly improved by using radiofrequency ablation at least on a short-term basis. This treatment can be administered as an outpatient procedure without complications related to speech, taste or swallowing.

Adult↗
PubMed2001

A new strategy for the detection of subtelomeric rearrangements.

We present a new strategy for the detection of subtelomeric rearrangements. This approach is based on two hybridizations with different probe sets. The first set consists of microdissected subtelomeric probes (each 5-10 megabases in size) labeled combinatorially employing 7 different fluorochromes. With this set, subtelomeric interchromosomal exchanges can be detected in a 24-color experiment. The second set comprises a second generation of subtelomeric PAC-, P1- and BAC-clones. Probes for p- and q-arms are labeled with two different colors. This second set detects small deletions; in addition it provides regional information, so that translocated material identified by the first probe set can be assigned to the p- or q-arm of a chromosome. The test has been evaluated in a blind study on a series of subtle translocations and deletions.

Chromosome Painting↗
PubMed2001

Properties of Manduca sexta chitinase and its C-terminal deletions.

Manduca sexta (tobacco hornworm) chitinase is a molting enzyme that contains several domains including a catalytic domain, a serine/threonine-rich region, and a C-terminal cysteine-rich domain. Previously we showed that this chitinase acts as a biopesticide in transgenic plants where it disrupts gut physiology. To delineate the role of these domains further and to identify and characterize some of the multiple forms produced in molting fluid and in transgenic plants, three different forms with variable lengths of C-terminal deletions were generated. Appropriately truncated forms of the M. sexta chitinase cDNA were generated, introduced into a baculovirus vector, and expressed in insect cells. Two of the truncated chitinases (Chi 1-407 and Chi 1-477) were secreted into the medium, whereas the one with the longest deletion (Chi 1-376) was retained inside the insect cells. The two larger truncated chitinases and the full-length enzyme (Chi 1-535) were purified and their properties were compared. Differences in carbohydrate compositions, pH-activity profiles, and kinetic constants were observed among the different forms of chitinases. All three of these chitinases had some affinity for chitin, and they also exhibited differences in their ability to hydrolyze colloidal chitin. The results support the hypothesis that multiple forms of this enzyme occur in vivo due to proteolytic processing at the C-terminal end and differential glycosylation.

Animals↗
PubMed2001

Gamma-radiation-induced G2 delay, apoptosis, and p53 response as potential susceptibility markers for lung cancer.

Gamma-radiation results in cell cycle arrest and apoptosis in a wide variety of cells. Cell cycle arrest provides time for the cell to repair damaged DNA before entering the next phase of the cycle. If the damage is severe and cannot be repaired, the cells undergo apoptosis. However, if the damaged cells continue to grow without repair or apoptosis, then carcinogenic transformation may occur. We hypothesized that individuals with inherited disruption in cell cycle control and/or apoptosis and/or DNA repair may be susceptible to lung cancer development. The cells from susceptible individuals would have a shorter G2 period and less apoptosis compared with cells from normal individuals upon exposure to gamma-radiation. To test this hypothesis, the following methods were used: (a) fluorescence-activated cell sorting method was used to measure apoptosis and G2 cell cycle delay; (b) the ELISA method was used to measure p53 protein expression levels in these cell lines; and (c) gamma-radiation-induced chromatid breaks were counted as a marker for DNA damage or repair. Next, gamma-radiation-induced G2 delay and apoptosis were tested in three lymphoblastoid cell lines to determine the dose response effect and optimal time points of gamma-radiation. Finally, these assays were tested in lymphoblastoid cell lines from 30 lung cancer patients and 22 healthy controls. We found a dose-response relationship for gamma-radiation-induced G2 delay and apoptosis. The optimal time points to detect differential G2 delay and apoptotic index were 10 h and 48 h after gamma-radiation, respectively. The mean G2 delay was 22.5% +/- 10.5% for the control cell lines and 14.71% +/- 8.8% for case cell lines (P < 0.01). The mean apoptotic index was 20.4% +/- 11.7% for the controls and 14.3% +/- 7.8% for the cases (P < 0.05). The controls had a significantly higher p53 response ratio and fewer chromatid breaks than the cases. We also found that a p53 increasing ratio was strongly related to cell cycle G2 delay (gamma = 0.413; P = 0.002) and chromatid breaks (gamma =0.384; P = 0.028). Therefore, we concluded that gamma-radiation-induced G2 delay, apoptosis, p53 increasing ratio, and chromatid breaks might potentially be used as susceptibility markers for lung cancer risk. A large epidemiology study is in progress to confirm these findings.

Adult↗
PubMed2001

Kinetics and morphologies of viscoelastic phase separation.

In this paper, the effects of relaxational bulk modulus and the average composition of polymers on the viscoelastic phase separation are investigated in detail. It is found that there are two typical morphologies, i.e., moving droplet phase and phase inversion, and the relaxation of the dynamical asymmetry and the amplification of the concentration fluctuation are responsible for the appearance and evolution of different morphologies of viscoelastic phase separation. It is found that, for the viscoelastic phase separation, the scattering function has two peaks. The growth exponents of the main and the secondary peaks in the late stage are almost the same and approximately 0.6, which also agrees with the experimental observations. On the other hand, the growth exponent of the secondary peak increased from approximately 0.42 to approximately 0.66 with increase of straight phi(0) from 0.275 to 0.4, in the intermediate stage.

Journal Article↗
PubMed2001

[Influence of low-molecular weight heparin on urine interleukin-6 in patients with proliferative glomerulonephritis].

OBJECTIVE: To explore the influence of low-molecular weight heparin (LMWH) on interleukin-6 (IL-6) in patients with proliferative glomerulonephritis, 24 patients which had been distinctly diagnosed by renal biopsy were randomly divided into a control group (n = 12) and a treatment group (n = 12). In addition to the treatments of the control group, the patients of the treatment group were given with LMWH by hypodermic injection for four weeks. The level of urine IL-6 was detected by radioimmunoassay (RIA). The results were that the level of urine IL-6 was higher in patients than that in healthy persons (n = 24); after the treatment, the level of urine IL-6 was significantly decreased both in the control and treatment group, but it was lower in the treatment group than that in the control group. The effect of LMWH on patients with proliferative glomerulonephritis may be associated with inhibiting the proliferation of mesangial cell and the accumulation of mesangial matrix.

Adolescent↗
PubMed2001

Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different alpha1-adrenoceptor subtypes.

In vivo studies have suggested that norepinephrine (NE) directly contributes to normal vascular wall growth and worsening of hypertrophy, atherosclerosis, and restenosis. However, it is unknown whether these effects are secondary to hemodynamic changes caused by systemic NE or alpha-adrenoceptor (AR) antagonists. Herein, we determined if NE directly stimulates growth of medial smooth muscle cells (SMCs) and adventitial fibroblasts (AFBs) that we have shown express alpha1-ARs in similar abundance. The rat aorta was isolated before injury, 4 days after, or 12 days after balloon injury, and maintained under circumferential tension in organ culture for 48 hours with 1 micromol/L NE. Intima-media and adventitia were separated and DNA content, protein synthesis, and protein content measured. In uninjured aorta, NE increased DNA and protein content similarly in adventitia, and increased only protein content in intima-media, suggesting AFB proliferation and SMC hypertrophy. In vessels isolated 4 or 12 days after injury, NE increased all 3 endpoints in both layers by up to 20-fold greater than in uninjured vessels. These effects were dose-dependent and were unaffected by alpha2- or beta-AR blockade (except increased DNA content in adventitia that was also inhibited by alpha2-AR blockade). Intima-media growth was blocked by KMD3213 (alpha1A-AR antagonist) and adventitial growth by AH11110A (alpha1B-AR antagonist), whereas BMY7378 (alpha1D-AR antagonist) had no effect. NE decreased SMC marker proteins (eg, alpha-smooth muscle actin and desmin) and augmented the changes induced by injury. These data suggest that prolonged stimulation of alpha1A- and alpha1B-ARs induces growth of SMCs and AFBs, respectively, that is significantly augmented by injury.

Angiotensin II↗
PubMed2001

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders.

BACKGROUND: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS: TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS: TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

Adolescent↗
PubMed2001

Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system.

Adenosine receptors (ADORs) in the enteric nervous system may be of importance in the control of motor and secretomotor functions. Gene expression and distribution of neural adenosine A1, A2a, A2b, or A3 receptors (Rs) in the human intestine was investigated using immunochemical, Western blotting, RT-PCR, and short-circuit current (I(sc)) studies. Adenosine A1R, A2aR, A2bR, or A3R mRNAs were differentially expressed in neural and nonneural layers of the jejunum, ileum, colon, and cecum and in HT-29, T-84, T98G, and Bon cell lines. A1R, A2aR, A2bR, and A3R immunoreactivities (IRs) were differentially expressed in PGP 9.5-immunoreactive neurons. A2bR IR occurs exclusively in 50% of submucosal vasoactive intestinal peptide (VIP) neurons (interneurons, secretomotor or motor neurons) in jejunum, but not colon; A2aR is also found in other neurons. A3R IR occurs in 57% of substance P-positive jejunal submucosal neurons (putative intrinsic primary afferent neurons) and less than 10% of VIP neurons. Western blots revealed bands for A3R at 44 kDa, 52 kDa, and 66 kDa. A2aR and A2bR are coexpressed in enteric neurons and epithelial cells. 5'-N-methylcarboxamidoadenosine or carbachol evoked an increase in I(sc). A2bR IR is more prominent than A2aR IR in myenteric neurons, nerve fibers, or glia. A1R is expressed in jejunal myenteric neurons and colonic submucosal neurons. Regional differences also exist in smooth muscle expression of ADOR IR(s). It is concluded that neural and nonneural A1, A2a, A2b, and A3Rs may participate in the regulation of neural reflexes in the human gut. Clear cell and regional differences exist in ADOR gene expression, distribution, localization, and coexpression.

Blotting, Western↗
PubMed2001

Bcl2-L-10, a novel anti-apoptotic member of the Bcl-2 family, blocks apoptosis in the mitochondria death pathway but not in the death receptor pathway.

By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain. The Bcl2-L-10 gene has been assigned to chromosome 15q21.2. Transfection experiments demonstrated that Bcl2-L-10 can block apoptosis induced by interleukin-3 withdrawal and Bax expression, by prevention of cytochrome C release, caspase-3 activation and mitochondrial membrane potential collapse. Bcl2-L-10 cannot block TNFalpha-induced apoptosis. Furthermore, both the BH4 domain and the transmembrane domain of Bcl2-L-10 are necessary for its suppressive action on cell death. Our results demonstrated that Bcl2-L-10 is a newly detected anti-apoptotic member of the Bcl-2 family and that it blocks apoptosis in the mitochondrial death pathway but not in the death receptor pathway.

Amino Acid Sequence↗
PubMed2001

Local costimulation reinvigorates tumor-specific cytolytic T lymphocytes for experimental therapy in mice with large tumor burdens.

Cytotoxic T cells recognize tumor Ags and destroy cancer cells in vitro. Adoptive transfer studies with transgenic T cells specific for tumor Ags have demonstrated that CTL are effective only in mice with small tumor burdens and thus appear to have limited potential in cancer immunotherapy. Here we used transgenic mice that express the TCR specific for an unmutated tumor Ag P1A and multiple lineages of P1A-expressing tumors to address this critical issue. We found that local costimulation, either by expression of B7-1 on the tumor cells or by local administration of anti-CD28 mAb 37N, reinvigorated the function of CTL specific for the tumor Ag, as it substantially increased the efficacy of CTL therapy for mice with large tumor burdens. Our study suggests that CTL-based immunotherapy can be manipulated to deal with large tumors.

Abatacept↗
PubMed2001

Complete inhibition of vascular endothelial growth factor (VEGF) activities with a bifunctional diabody directed against both VEGF kinase receptors, fms-like tyrosine kinase receptor and kinase insert domain-containing receptor.

Vascular endothelial growth factor (VEGF) binds to and mediates its activity mainly through two tyrosine kinase receptors, VEGF receptor 1 [or fms-like tyrosine kinase receptor (Flt-1)] and VEGF receptor 2 [or kinase insert domain-containing receptor (KDR)]. Numerous studies have shown that overexpression of VEGF and its receptor plays an important role in tumor-associated angiogenesis and hence in both tumor growth and metastasis. We demonstrated previously that antagonistic antibodies to KDR specifically inhibited VEGF-stimulated receptor activation, cell migration, and endothelial cell mitogenesis. Here we constructed a recombinant bifunctional diabody that is capable of blocking both Flt-1 and KDR from binding to their ligands, including VEGF and placenta growth factor (PlGF). The diabody was expressed in Escherichia coli and purified by single-step affinity chromatography. The diabody retained the capacity to bind both KDR and Flt-1 and effectively blocked interaction between KDR and VEGF, Flt-1 and VEGF, and Flt-1 and PlGF. Furthermore, the diabody is a stronger inhibitor than its parent antibodies to VEGF-stimulated mitogenesis of human endothelial cells, as well as both VEGF- and PlGF-induced migration of human leukemia cells. Taken together, our results suggest that dual receptor blockade with the bifunctional diabody may prove to be a more efficient approach in inhibiting VEGF-stimulated angiogenesis.

3T3 Cells↗
PubMed2001

A new functional domain of Bcl6 family that recruits histone deacetylases.

The proto-oncogene Bcl6 and its family gene, BAZF, encode a sequence-specific transcriptional repressor which contains the BTB/POZ domain in NH(2)-terminal region and zinc finger motifs in COOH-terminal region. The BTB/POZ domain and the middle portion of Bcl6 and BAZF are known to display transrepressor activity. Since we have identified the identical 17-amino acid (aa) sequence in the middle portion of Bcl6 and BAZF, the 17aa region may be another repressive domain of the middle portion. The reporter gene assay indicates that the 27aa sequence including the 17aa region recruits histone deacetylases to express transrepressor activity. Furthermore, overexpression of Bcl6 or Bcl6(POZ-) (Bcl6 deleted with the BTB/POZ domain) induced apoptosis in NIH3T3 cells, and the apoptosis was inhibited by the addition of histone deacetylase inhibitor in the culture. However, apoptosis was not induced in NIH3T3 cells by overexpression of Bcl6(POZ-) deleted with the 17aa region. These results indicate that the 17aa region in the middle portion of Bcl6 is a functional domain of transrepressor activity and is responsible for inducibility of apoptosis in NIH3T3 cells.

3T3 Cells↗
PubMed2001

Salicylate uniquely induces a 27-kDa protein in tubercle bacillus.

Salicylate was found to uniquely induce a 27-kDa protein in Mycobacterium tuberculosis complex organisms but not in Mycobacterium smegmatis or Escherichia coli. The structural analogue antitubercular para-amino-salicylate also induced the 27-kDa protein but to a somewhat lower level than salicylate. Other structural analogues such as benzoic acid and acetyl salicylic acid (aspirin) did not induce the 27-kDa protein. Western blot analysis indicated that the 27-kDa protein was localized mainly in the cytoplasm. The 27-kDa protein was not expressed at different growth phases in the absence of salicylate. The 27-kDa protein was identified as a putative benzoquinone methyltransferase (Rv0560c), which has several homologues in the M. tuberculosis genome. The cloned 27-kDa gene was found to express constitutively in E. coli, M. smegmatis and BCG with or without salicylate.

Aminosalicylic Acid↗
PubMed2001

Design and synthesis of potent C(2)-symmetric diol-based HIV-1 protease inhibitors: effects of fluoro substitution.

Implementation of derivatized carbohydrates as C(2)-symmetric HIV-1 protease inhibitors has previously been reported. With the objective of improving the anti-HIV activity of such compounds, we synthesized a series of fluoro substituted P1/P1' analogues. These compounds were evaluated for antiviral activity toward both wild type and mutant virus. The potency of the analogues in blocking HIV-1 protease was moderate, with K(i) values ranging from 1 to 7 nM. Nonetheless, compared to the parent nonfluorous inhibitors, a majority of the compounds exhibited improved antiviral activity, for example the 3-fluorobenzyl derivative 9b, which had a K(i) value of 7.13 nM and displayed one of the most powerful antiviral activities in the cellular assay of the series. Our results strongly suggest that fluoro substitution can substantially improve antiviral activity. The X-ray crystal structures of two of the fluoro substituted inhibitors (9a and 9f) cocrystallized with HIV-1 protease are discussed.

Amides↗